gelsemine and koumine

Gelsemium is a toxic flowering plant of the Gelsemiaceae family. It is used to treat skin diseases in China, and it is an important medicinal and homeopathic plant in North America. Up to now, more than 200 compounds have been isolated and reported from Gelsemium. More than 120 of these are indole alkaloids, including the main components, koumine, gelsemine and humantenmine which produce the pharmacological and toxicological effects of Gelsemium. However, their clinical application their limited by its narrow therapeutic window. Therefore, it is very important to study the metabolism and disposition of indole alkaloids from Gelsemium before their clinical application. This paper reviews all the reports on the metabolism and disposition of alkaloids isolated from Gelsemium at home and abroad.. The metabolism and disposition of alkaloids from Gelsemium were searched by the Web of Science, NCBI, PubMed and some Chinese literature databases.. Only koumine, gelsemine and humantenmine have been reported, and few other alkaloids have been described. These studies indicated that the three indole alkaloids are absorbed rapidly, widely distributed in tissues, extensively metabolized and rapidly eliminated. There are species differences in the metabolism of these alkaloids, which is the reason for the differences in their toxicity in animals and humans.. This review not only explains the pharmacokinetics of indole alkaloids from Gelsemium but also facilitates further study on their metabolism and mechanism of toxicity.

Topics: Alkaloids; Animals; Gelsemium; Humans; Indole Alkaloids; Plant Extracts

Gelsemium, a small genus of flowering plant from the family Loganiaceae, comprises five species including the popular Gelsemium sempervirens Ait. and Gelsemium elegans Benth., which are indigenous to North America and China/East Asia, respectively. Approximately 120 alkaloids have been isolated and identified from Gelsemium, with the predominant indole alkaloids including gelsemine, koumine, gelsemicine, gelsenicine, gelsedine, sempervirine, koumidine, koumicine and humantenine. Gelsemine is the principal active alkaloid in G. sempervirens Ait., and koumine and gelsemine are the most and second-most dominant alkaloids in G. elegans Benth. Gelsemium extract and its active alkaloids serve a variety of biological functions, including neurobiological, immunosuppressive and antitumor effects, and have traditionally been used to treat pain, neuralgia, anxiety, insomnia, asthma, respiratory ailments and cancers. This review focuses on animal-based studies of Gelsemium as a pain treatment and its mechanism of action. In contrast to morphine, when administered intrathecally and systemically, koumine, gelsemine and gelsenicine have marked antinociception in inflammatory, neuropathic and bone cancer pains without inducing antinociceptive tolerance. Gelsemium and its active alkaloids may produce antinociception by activating the spinal α3 glycine/allopregnanolone pathway. The results of this review support the clinical use of Gelsemium and suggest that its active alkaloids may be developed to treat intractable and other types of pain, preferably after chemical modification. However, Gelsemium is a known toxic plant, and its toxicity limits its appropriate dosage and clinical use. To avoid or decrease the side/toxic effects of Gelsemium, an individual monomer of highly potent alkaloids must be selected, or alkaloids that exhibit greater α3 glycine receptor selectivity may be discovered or modified.

Topics: Alkaloids; Analgesics; Animals; Gelsemium; Indole Alkaloids; Mice; Molecular Structure; Pain; Pregnanolone; Rats; Receptors, Glycine

Topics: Alkaloids; Chromatography, High Pressure Liquid; Gelsemium; Humans; Indole Alkaloids; Tandem Mass Spectrometry

We present a case of fatal poisoning from accidental ingestion of Gelsemium elegans (G. elegans), a rarely toxic plant. A 41-year-old man was found dead, at his home, 6 h after drinking homemade herbal liqueur during lunch. Autopsy and routine toxicological analyses identified neither significant pathological findings nor routine poisons. However, a local botanist revealed that the homemade herbal liqueur contained G. elegans, a poisonous plant specific to Asia. To ascertain whether the decedent had ingested G. elegans, we performed liquid chromatography-mass spectrometry (LC-MS) and found two alkaloids (gelsemine and koumine) in his blood, gastric contents, as well as the suspected herbal liqueur. The cause of death was therefore confirmed to be G. elegans poisoning. Case reports of fatal poisoning due to ingestion of G. elegans are quite rare in English. Therefore, the present case broadens the scope on the possibility of death due to ingestion of G. elegans for forensic pathologists and toxicologists.

Topics: Accidents; Adult; Alkaloids; Beverages; Chromatography, Liquid; Fatal Outcome; Gastrointestinal Contents; Gelsemium; Humans; Indole Alkaloids; Male; Mass Spectrometry; Plants, Toxic

Gelsemium elegans (G. elegans) has been used in traditional Chinese medicine. This plant is highly toxic to humans, but can promote the growth of pigs and goats in the veterinary clinic. It is a very complex mixture containing tens or hundreds of different components. Therefore, multiple-component pharmacokinetic studies of G. elegans are a major challenge due to the lack of authentic standards of the components. The purpose of this study was to investigate the plasma pharmacokinetics of multiple components after a single oral dose of G. elegans in goat using a sensitive ultra-performance liquid chromatography coupled to tandem mass spectrometry method for the simultaneous semiquantification of multiple alkaloids without standards. The method was validated in terms of the specificity, LOD, LOQ, linearity, accuracy, precision and matrix effects. To validate the global pharmacokinetic characteristics, the results obtained from the semiquantitative analysis of three authentic compounds (gelsemine, koumine and humantenmine) were compared with the absolute quantification from our recently published method. The results showed that the two methods had similar analytical results, and the obtained values of Tmax, T1/2 and MRT0-t of the three alkaloids were similar between the two methods. In addition, the values of Cmax and AUC0-t of the three alkaloids after normalization were close to the real values, which indicated that this semiquantitative method could be used in the pharmacokinetic study of multiplecomponents. Then the pharmacokinetic parameters of 23 other G. elegans alkaloids in goats were obtained. The results suggested that the gelsedine-type alkaloids were the major active ingredients that predict and explain the efficacy and toxicity of G. elegans.

Topics: Alkaloids; Animals; Chromatography, Liquid; Gelsemium; Goats; Humans; Indole Alkaloids; Plant Extracts; Swine; Tandem Mass Spectrometry

The present paper describes a novel two-dimensional liquid chromatography (2D-LC) system, which is comprised of a first-dimensional ion exchange chromatography (IEX1) column, trap column, and second-dimensional reversed-phase chromatography (RP2) column system. The biological sample is separated by the first-dimensional LC using an IEX column to remove interferences. The analytes are transferred to the trap column after heart-cutting. Then, the analytes are transferred to the second-dimensional LC using an RP2 column for further separation and ultraviolet detection. This 2D-LC system can offer a large injection volume to provide sufficient sensitivity and exhibits a strong capacity for removing interferences. Here, the determination of three monoterpene indole alkaloids (MIAs; gelsemine, koumine, and humantenmine) from Gelsemium in biological matrices (plasma, tissue, and urine) was used this 2D-LC system. After a rapid and easy sample preparation method based on protein precipitation, the sample was injected into the 2D-LC. The method was developed and validated in terms of the selectivity, LOD, LOQ, linearity, precision, accuracy, and stability. The sample preparation time for the three MIAs was 15 min. The LOD for these compounds was 10 ng/mL, which was lower than the developed HPLC methods. The results showed that this method had good quantitation performance and allowed the determination of gelsemine, koumine, and humantenmine in biological matrices. The method is rapid, exhibits high selectivity, has good sensitivity, and is low-cost, thus making it well-suited for application in the pharmaceutical and toxicological analysis of Gelsemium. Graphical abstract.

Topics: Alkaloids; Chromatography, Ion Exchange; Chromatography, Reverse-Phase; Indole Alkaloids; Limit of Detection; Reference Standards; Reproducibility of Results; Spectrophotometry, Ultraviolet

Two optical isomers, +/- gelsemine (1, 2), together with one known compound were isolated from the whole plant of

Topics: Alkaloids; Animals; Gelsemium; Indole Alkaloids; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; PC12 Cells; Plant Extracts; Rats

Topics: Administration, Oral; Alkaloids; Animals; Chromatography, High Pressure Liquid; Gelsemium; Indole Alkaloids; Linear Models; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry

Topics: Alkaloids; Animals; Chromatography, Liquid; Drug Stability; Indole Alkaloids; Limit of Detection; Linear Models; Reproducibility of Results; Swine; Tandem Mass Spectrometry

To establish a LC-MS/MS method which is accurate and sensitive for determination of koumine, gelsemine, and gelsenicine in biological samples and to verify the method.. Strychnine was used as internal standard. Analytes in blood, urine and liver with 1% sodium hydroxide solution were extracted by ethyl acetate. Chromatographic separation was achieved on a ZORBAX SB-C₁₈ column （150 mm×2.1 mm, 5 μm）, and gradient elution was performed with the buffer solution of methanol-20 mmol/L ammonium acetate （including 0.1% formic acid and 5% acetonitrile） as mobile phase. Qualitative and quantitative analysis was performed in the multiple reaction monitoring mode coupled with an electrospray ionization source under positive ion mode（ESI⁺）.. The method is selective, sensitive and suitable for simultaneous determination of koumine, gelsemine and gelsenicine in body fluids and tissues, which offering technical support for clinical diagnosis and treatment and forensic toxicological analysis of

Topics: Alkaloids; Chromatography, High Pressure Liquid; Chromatography, Liquid; Forensic Toxicology; Formates; Humans; Indole Alkaloids; Liver; Reproducibility of Results; Strychnine; Tandem Mass Spectrometry

To investigate the effects of alkaloid monomers from Gelsemium elegans on proliferation of HepG2 cell in vitro and the possible mechanism.. MTT assay was used to measure the inhibitory of three alkaloid monomers on HepG2 cell in vitro. The most effective fraction was chosen to test whether the effect was in time-and dose-dependent manner. The morphological changes were observed by the light microscope and the cell cycle alteration through the flow cytometric assay. The activity of Caspase-3, Caspase-8 and Caspase-9 were detected by a Caspases colorimetric assay kit.. The results showed that koumine, Gelsemine and Gelsenicine could significantly inhibit the proliferation of HepG2 cell and Gelsenicine, the most effective fraction, was clearly in dose- and time-dependent manners, while exhibited low cytotoxicity to the Vero cell. The cell treated with Gelsenicine for 48 h showed distinctive morphological changes. The cells treated with 200 and 400 microg/mL shrinked and fell off from the bottom. At the same time, the cells were arrested at S phase and the apoptosis increased apparently. The activity of Caspase-3, Caspase-8 and Caspase-9 was increased in a dose-dependent manner.. Three alkaloid monomers from Gelsemium elegans, especially Gelsenicine, could inhibit proliferation of HepG2 cell obviously. The mechanism may be related to cell cycle arrest and activation of Caspase-3, Caspase 8 and Caspase-9.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Hepatocellular; Caspases; Cell Cycle; Cell Proliferation; Dose-Response Relationship, Drug; Flow Cytometry; Hep G2 Cells; Humans; Indole Alkaloids; Liver Neoplasms; Loganiaceae; Time Factors

Alkaloids in Gelsemium elegans possess a variety of therapeutic properties, including tumor suppression, analgesic and anti-inflammatory effects. In China, G. elegans has been used for centuries to treat a variety of medical conditions, including chronic pain and skin ulcer. Methods currently used to separate the active components of G. elegans are time-consuming and have low recovery. In the present study, we used pH-zone-refining counter-current chromatography to separate major alkaloids from a crude extract of G. elegans. The two-phase solvent system was methyl tert-butyl ether (MtBE)/acetonitrile/water (3:1.5:4, v/v). Triethylamine (20 mM) was added to the upper organic stationary phase as a retainer. Hydrochloric acid (10 mM) was added to the lower aqueous phase as an eluter. From 1.5 g of crude extract, we obtained 312 mg gelsemine, 420 mg koumine and 195 mg gelsevirine, with purities at 94.8%, 95.9% and 96.7%, respectively, which were determined by HPLC at 256 nm. The chemical identity of the isolated compounds was verified by electrospray ionization-mass spectrometry (ESI-MS), ¹H NMR and ¹³C NMR. These results demonstrated that pH-zone-refining counter-current chromatography is an effective method to separate and purify major alkaloids from G. elegans.

Topics: Alkaloids; Countercurrent Distribution; Drugs, Chinese Herbal; Gelsemium; Hydrogen-Ion Concentration; Indole Alkaloids